RADIATION CATARACTOGENESIS

放射性白内障发生

• 批准号: 3256955
• 负责人: BASIL V WORGUL
• 金额: $ 21.79万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-09-01 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3256955
• 关键词: X ray; autoradiography; cataract; cell differentiation; cell growth regulation; cellular pathology; chromosome disorders; cytogenetics; cytotoxicity; electron microscopy; epithelium; fresh water environment; histochemistry /cytochemistry; histopathology; hormone regulation /control mechanism; microscopy; radiation dosage; radiation hazard; radiation sensitivity; radiobiology

The long range goal of the proposed studies is to elucidate the mechanism of radiation cataractogenesis. To do so the work will focus on three aspects of the problem. 1. The site of the initial injury. 2. The nature of the injury. 3. The manner in which the injury is expressed as cataract. The hypothesis to be tested assigns the initial insult to the genome of the lens epithelial cell. The cataract is the result of the expression of that injury during lens fiber differentiation. The studies directed at the first question will include preferential sensitization of the DNA of lens cell subpopulation using BrdU substitution techniques. Endocrinological intervention experiments are designed to dissect the roles of growth and differentiation in the radiation response. Investigations will be conducted to attempt to confirm that the bird lens, heretofore thought to be radioresistant, does develop radiocataracts. It appears that the unique anatomy, which accounts for the exaggerated period before lens epithelial cells become fibers, is responsible, thus corroborating the role of the epithelium in radiation cataract development. Radiation genotoxicity will be assayed by sister chromatid exchange and chromosomal aberration analyses. Both cytogenetic methods have been adapted by our laboratory to lens research. In addition the distinctive nature of heavy particle irradiation (500 MeV Argon) will be fully exploited to clarify the nature of other damage at the cellular and subcellular level. Cell kinetic and cytopathological studies willl aim at characterizing the nuances of the manner in which the affected epithelial cells transduce the injury into a clinically detectable opacity. The work will focus on perturbations in the lens epithelial cell cycle and differentiation. The latter aspect will be monitored by analyzing possible effects on the cytoskeleton and the crystallins within individual cells known to be damaged. The findings will contribute greatly to our understanding of cortical cataractogenesis of varying etiology, including age, and will have direct application in radiation risk assessments from radiation therapy, occupational exposure and in the space program.

拟议研究的长期目标是阐明其机制 放射性白内障的发生。 为此，工作重点将集中在三方面 问题的各个方面。 1. 最初受伤的部位。 2. 性质 的伤害。 3. 伤害的表达方式为 白内障。 要检验的假设将最初的侮辱分配给 晶状体上皮细胞的基因组。 白内障的结果是 晶状体纤维分化过程中损伤的表达。 针对第一个问题的研究将包括优先 使用 BrdU 替代对晶状体细胞亚群 DNA 进行敏化 技术。 内分泌干​​预实验旨在 剖析生长和分化在辐射响应中的作用。 将进行调查以试图确认鸟类镜头， 迄今为止，人们认为它具有抗辐射性，但它确实会导致放射性白内障。 它 似乎独特的解剖结构，这解释了夸张的时期 在晶状体上皮细胞变成纤维之前，负责，因此 证实上皮在放射性白内障发展中的作用。 辐射遗传毒性将通过姐妹染色单体交换进行测定 染色体畸变分析。 两种细胞遗传学方法均已 由我们的实验室改编用于镜片研究。 另外还有特色鲜明的 重粒子线辐照（500 MeV 氩气）的性质将得到充分 用于阐明细胞和细胞其他损伤的性质 亚细胞水平。 细胞动力学和细胞病理学研究将旨在表征 受影响的上皮细胞转导的方式的细微差别 损伤变成临床上可检测到的混浊。 工作将重点 晶状体上皮细胞周期和分化的扰动。 这 将通过分析对后一方面的可能影响进行监测 已知单个细胞内的细胞骨架和晶状体蛋白 损坏的。 这些发现将极大地促进我们对皮质的理解 白内障的发生有不同的病因，包括年龄，并且会直接影响 在放射治疗的辐射风险评估中的应用， 职业暴露和太空计划。